Luboslav Stárka

Publications (325) View all

• Article: Dehydroepiandrosterone in the type 1 diabetes mellitus.

  M Duskova, H Hruskovicova, M Hill, L Starka
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  ABSTRACT: Dehydroepiandrosterone (DHEA) is believed to exert, besides others, positive effects on the insulin resistance or its secretion and glucose metabolism. There are several reports dealing with the DHEA levels and its effects in the type 2 diabetes mellitus, but less information is available on the type 1 diabetic subjects. Recently, a report dealing with the lack of the age-dependent decline of the DHEA levels in the type 2 diabetic subjects was published. The aim of the present study was to answer the question whether a comparable change in the aging pattern of the DHEA and its sulphate could be detected in the type 1 diabetes mellitus. The data regarding the DHEA and dehydroepiandrosterone sulphate (DHEA-S) concentrations in the serum obtained from 116 patients with the type 1 diabetes mellitus and 259 controls were gathered from the database of the Institute of Endocrinology (Prague, Czech Republic). No significant differences in the level of the DHEA-S were found between the type 1 diabetics and controls either in men or women. However, lower DHEA levels were found in the type 1 diabetic women, but not in men. The age-dependent declines of both the DHEA and DHEA-S were similar to those in controls. In contrast to the type 2 diabetes, the levels of DHEA-S in the type 1 diabetic patients were practically identical with those in controls. In contrast to men, in women, the DHEA basal levels were lower than those seen in controls. The age dependence of both hormones followed the pattern of the decline in controls.
  Endocrine regulations 04/2012; 46(2):67-71.
• Article: 7-hydroxylated derivatives of dehydroepiandrosterone as possibly related to menstrual mood change in healthy women.

  M Duskova, K Simunkova, M Hill, L Starka
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  ABSTRACT: Mood changes occur often in the luteal phase of menstrual cycle. Steroids modulating GABAA and NAMD receptors in the brain, namely allopregnanolone, were suggested as a factor of premenstrual syndrome. Another neurosteroid influencing the well-being is dehydroepiandrosterone. In the past decade it was shown by several authors that some dehydroepiandrosterone derivatives, especially those with 7-hydroxy- or 7-oxo group, exert a higher activity than dehydroepiandrosterone itself. It was also reasonable to see whether the levels of circulating 7-hydroxy-derivatives of dehydroepiandrosterone differ in the follicular and luteal phase of the menstrual cycle. Steroids known to exert neuroprotective effects, namely 7α- and 7β-hydroxy-dehydroepiandrosterone, 5-androstene-3β,7α,17β-triol and 5-androstene-3β,7β,17β-triol, were determined in midfollicular and midluteal phase of the menstrual cycle of 22 healthy women with a regular menstruation cycle. Whereas the maternal steroids, dehydroepiandrosterone and androstene-3β,17β-diol showed no significant difference between the phases of menstrual cycle, the levels of their 7-hydroxylated metabolites were significantly lower in the luteal phase. It is suggested that the observed decrease of 7-hydroxylated metabolites during the luteal phase may be a factor related to the etiopathogenesis of mood change and neurocognitive disturbances, which are known to be more accented in that particular phase of the menstrual cycle.
  Endocrine regulations 07/2011; 45(3):131-7.
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  Available from: Luboslav Stárka

  Article: Changes of metabolic profile in men treated for androgenetic alopecia with 1 mg finasteride.

  M Duskova, M Hill, L Starka
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  ABSTRACT: Androgenetic alopecia is recognized as a risk factor for cardiovascular diseases, glucose metabolism disorders, and benign prostate hyperplasia and/or carcinoma. Finasteride, used for treatment of androgenetic alopecia at a dose of 1mg/day, is an effective inhibitor of type II 5alpha-reductase, the enzyme responsible for the reduction of testosterone to dihydrotestosterone. Recent studies reported that dihydrotestosterone, among other activities, might play some role in visceral fat metabolism. It thus seemed reasonable to examine whether finasteride treatment of androgenetic alopecia ameliorates some features of metabolic syndrome frequently seen associated with this condition. We examined 12 men with premature balding (defined as frontoparietal and vertex hair loss before age 30 with alopecia defined as grade 3 vertex or more on the Norwood-modified Hamilton alopecia classification). Hormonal levels and metabolic parameters were determined and insulin tolerance tests performed for all individuals. Finasteride (1 mg/day) was administrated for 12 months. The hormonal profile and lipid spectrum were monitored after 4, 8 and 12 months of treatment and insulin tolerance tests were repeated after 12 months of the treatment. After treatment with finasteride the expected changes in the steroid spectrum were seen, namely a decrease in dihydrotestosterone and increase in testosterone, androstenedione and free testosterone index. We observed an initial increase in total cholesterol and HDL- and LDL-cholesterol, which stabilized with prolonged treatment. We founded a significant decrease in glycated hemoglobin HbA1c and insulin resistance measured using rate constant for plasma glucose disappearance (kITT) showed only a borderline decrease. Finasteride is an efficient 5alpha-reductase inhibitor even at low doses of 1 mg/day. In men treated with this dose for 12 months, we observed mild differences in metabolic profile with slight amelioration of glucose metabolism regulation.
  Endocrine regulations 01/2010; 44(1):3-8.
• Article: The steroid metabolome in lamotrigine-treated women with epilepsy.

  Martin Hill, Jana Vrbíková, Jana Zárubová, Radmila Kancheva, Marta Velíková, Lyudmila Kancheva, Jana Kubátová, Michaela Dušková, Petr Marusič, Antonín Pařízek, Luboslav Stárka
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  ABSTRACT: Epilepsy in women may be associated with reproductive disorders and alterations in serum steroid levels. Some steroids can be induced by epilepsy and/or treatment with antiepileptic drugs; however, there are still limited data available concerning this effect on the levels of other neuroactive steroid metabolites such as 3a-hydroxy-5a/b-reduced androstanes. To evaluate steroid alterations in women with epilepsy (WWE) on lamotrigine monotherapy. Eleven WWE and 11 age-matched healthy women underwent blood sampling in both phases of their menstrual cycles (MCs). The steroid metabolome, which included 30 unconjugated steroids, 17 steroid polar conjugates, gonadotropins, and sex hormone-binding globulin (SHBG), was measured using gas chromatography-mass spectrometry (GC-MS) and radioimmunoassay (RIA). WWE had lower cortisol levels (status p<0.001), but elevated levels of unconjugated 17-hydroxypregnenolone (status p<0.001). Progesterone was higher in the follicular menstrual phase (FP) in WWE than in the controls (status×menstrual phase p<0.05, Bonferroni multiple comparisons p<0.05), whereas 17-hydroxyprogesterone was higher in WWE in both menstrual phases (status p<0.001). The steroid conjugates were mostly elevated in WWE. The levels of 5α/β-reduced androstanes in WWE that were significantly higher than the controls were etiocholanolone (status p<0.001), 5α-androstane-3α,17β-diol (status p<0.001), and the 5α/β-reduced androstane polar conjugates (status p<0.001). WWE showed a trend toward higher circulating 3α-hydroxy-5α/β-reduced androstanes, increased activity of 17α-hydroxylase/17,20 lyase in the Δ(5)-steroid metabolic pathway, and increased levels of the steroid polar conjugates.
  Steroids 07/2011; 76(12):1351-7. · 2.83 Impact Factor
• Article: Effects of valproate and carbamazepine monotherapy on neuroactive steroids, their precursors and metabolites in adult men with epilepsy.

  Martin Hill, Jana Zárubová, Petr Marusič, Jana Vrbíková, Marta Velíková, Radmila Kancheva, Lyudmila Kancheva, Jana Kubátová, Michaela Dušková, Ludmila Zamrazilová, Hana Kazihnitková, Kateřina Simůnková, Luboslav Stárka
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  ABSTRACT: Only limited data is available concerning the role of unconjugated Δ(5) C19-steroids and almost no data exists regarding the neuroactive C21 and C19 3α-hydroxy-5α/β-metabolites in men with epilepsy. To evaluate the alterations in serum neuroactive steroids and related substances in adult men with epilepsy on valproate and carbamazepine monotherapy, we have measured 26 unconjugated steroids, 18 steroid polar conjugates, gonadotropins and sex hormone binding globulin (SHBG) in 6 and 11 patients on valproate and carbamazepine monotherapy, respectively, and in 19 healthy adult men, using the GC-MS and immunoassays. Decreased testosterone, free androgen index, free testosterone, androstenediol, 5α-androstane-3α,17β-diol (androstanediol), androsterone, epiandrosterone, DHEA, 7β-hydroxy-DHEA, and DHEAS levels were associated with epilepsy per se. Valproate (VPA) therapy increased 5α-dihydrotestosterone, androsterone, epiandrosterone, DHEA, DHEAS, and 7β-hydroxy-DHEA levels. Decrease in pregnenolone and 17-hydroxypregnenolone were associated with epilepsy with no effect of antiepileptic drugs (AEDs). Alternatively, the increase in progesterone levels was linked to epilepsy and VPA further increased progesterone levels. Reduced steroid 20α-hydroxy-metabolites and cortisol were connected with epilepsy without an effect of AEDs. Carbamazepine induced only slight decrease in isopregnanolone, 5α,20α-tetrahydroprogesterone, and androstanediol levels.
  The Journal of steroid biochemistry and molecular biology 10/2010; 122(4):239-52. · 2.66 Impact Factor